Vascular imaging of the brain has played an important role in the management of a variety of brain disorders, such as intracranial stenosis, carotid artery stenosis, stroke, small vessel diseases, brain tumor, traumatic brain injury, Moyamoya disease, and drug-addictive conditions. Both baseline examinations and stress tests are commonly used in clinical practice and they provide complementary information. However, a major limitation is that collection of all of this information requires separate scans and, in some cases, separate visits. This limitation increases patient burden and significantly escalates the cost of care. Therefore, the goal of this R21 project is to develop advanced methods to perform a one-stop-shop imaging of vascular physiology that provides multiple domains of information. The proposed technique uses the time of a single scan to apply both O2 and CO2 gas inhalation tasks, which provide baseline and vascular reactivity information, respectively, and tracks the gas bolus to obtain transit time information, as well as extracting functional connectivity networks from the same dataset. CO2 and O2 are important components of our body's metabolic pathway, but they also have interesting vascular properties in the context of brain perfusion imaging. CO2 is a potent vasodilator and can be used to measure vascular reactivity. O2 is inert to blood vessels but its inhalation changes BOLD MRI signal, which allows the estimation of an index of baseline cerebral blood volume (CBV). Furthermore, with our novel breathing paradigm, both CO2 and O2 tasks can be completed concomitantly with the duration of one scan. Additionally, inhaled O2 and CO2 can serve as boluses in the blood stream for the measurement of bolus time-to-peak (TTP). Finally, BOLD MRI data acquired during gas-inhalation tasks can be used for the analysis of functional connectivity networks of the brain. Therefore, our central hypothesis is that a single MRI scan with the proposed procedure will simultaneously provide baseline CBV, cerebrovascular reactivity, time-to-peak, and resting-state functional connectivity. We will first conduct development of the technique in healthy controls (in Aim 1), then perform validation and initial clinical demonstration in patients with intracranial arterial stenosis (in Aim 2). Impact: The impact on clinical practice is that cerebrovascular patients who require both baseline and reactivity assessment will be able to complete the whole procedure with just one visit of 10-15 minutes (as opposed to two visits of 90 minutes each). Additionally, patients who are allergic to conventional contrast agent will have access to an alternative contrast agent (i.e. O2 and CO2 gases) for their vascular imaging needs.